chr17-32021177-C-G

Variant names:

• chr17-32021177-C-G
• rs780110966
• ENST00000341671.12:c.31C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_052888.3(LRRC37B):​c.31C>G​(p.Pro11Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,613,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: LRRC37B NM_052888.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.19
• Publications: 0 publications found

Genes affected

LRRC37B (HGNC:29070): (leucine rich repeat containing 37B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09072089).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052888.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC37B	NM_001321350.2	MANE Select	c.1-216C>G		intron	N/A	NP_001308279.1	F5H5K1
	LRRC37B	NM_052888.3		c.31C>G	p.Pro11Ala	missense	Exon 1 of 12	NP_443120.2	Q96QE4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC37B	ENST00000341671.12	TSL:1	c.31C>G	p.Pro11Ala	missense	Exon 1 of 12	ENSP00000340519.7	Q96QE4-1
	LRRC37B	ENST00000584368.5	TSL:1	c.31C>G	p.Pro11Ala	missense	Exon 1 of 10	ENSP00000463081.2	J3KTP0
	LRRC37B	ENST00000543378.7	TSL:2 MANE Select	c.1-216C>G		intron	N/A	ENSP00000443345.2	F5H5K1

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152242 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 250358 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000363 AC: 53 AN: 1461148 Hom.: 0 Cov.: 32 AF XY: 0.0000482 AC XY: 35 AN XY: 726886

African (AFR) AF: 0.0000299 AC: 1 AN: 33450

American (AMR) AF: 0.0000224 AC: 1 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5204

European-Non Finnish (NFE) AF: 0.0000441 AC: 49 AN: 1111984

Other (OTH) AF: 0.0000332 AC: 2 AN: 60326

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152242 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74374

African (AFR) AF: 0.00 AC: 0 AN: 41464

American (AMR) AF: 0.000458 AC: 7 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.52
DANN	Benign	0.58
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0034	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	2.0	M
PhyloP100		-2.2
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.033
Sift	Benign	0.17	T
Sift4G	Benign	0.19	T
Polyphen		0.92	P
Vest4		0.098
MutPred		0.48		Gain of helix (P = 0.027)
MVP		0.40
MPC		0.047
ClinPred		0.044	T
GERP RS		-2.2
PromoterAI		-0.0074	Neutral
Varity_R		0.037
gMVP		0.082

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs780110966; hg19: chr17-30348196;